Featured PGRN Investigators

​Dr. Mushiroda’s primary scientific interest is to identify pharmacogenomics (PGx) biomarkers that can predict efficacy or risk of adverse drug reactions for various drugs by genomic analyses. The genome-wide association study (GWAS) presently stands as a standard method in the genomic analyses but can explain only a part of the association of genomic variations with drug responses. Pharmacokinetic variabilities are often responsible for inter-individual differences in drug responses.

​Thus, genetic variations in “Pharmacogenes” encoding proteins involved in pharmacokinetics, drug-metabolizing enzymes and drug transporters, are of increasing importance for identification of PGx biomarkers. However, it has been difficult to examine variations in the pharmacogenes because most of the genes are located within complex genomic regions.

Dr. Mushiroda’s team has developed a targeted next generation sequencing (NGS) panel of 100 pharmacogenes related to pharmacokinetics based on multiplex-PCR, which can analyze common and rare variants comprehensively and accurately, and thus will be effective for the identification of PGx biomarkers (https://doi.org/10.18632/oncotarget.25712).

​Since his mission is implementation of PGx testing, his team conducts prospective clinical trials to demonstrate the clinical utility of genetic tests using the PGx biomarkers identified by their basic research. If successful, this will lead to use of the PGx biomarkers as in-vitro diagnostics under the health insurance system. Recently, they completed a prospective PGx clinical trial, GENCAT that showed clinical utility of HLA-A*31:01 screening for patients who needed treatment with an antiepileptic drug carbamazepine (https://jamanetwork.com/journals/jamaneurology/article-abstract/2676800).To tackle the issue of PGx regionally, in 2012 RIKEN established the South East Asian Pharmacogenomics Research Network (SEAPharm) together with five other Asian countries (Korea, Indonesia, Malaysia, Taiwan, and Thailand). Membership has been steadily increasing, with Singapore joining in 2014, and Vietnam in 2016. Last year, SEAPharm accepted three newcomers, Nepal, Laos and the Philippines, on the team. The aim of the collaboration is to identify PGx biomarkers associated with adverse drug reactions, such as skin rash induced by anti-epileptics and antibiotics, and hepatic injury induced by anti-tuberculosis agents. In addition, a new project has been started, which involves targeted NGS of genomic DNA from 1,000 people from 10 countries to clarify the genetic diversity of drug-metabolizing enzymes and drug transporters in Southeast Asian populations.